title: Design of Small Molecules with HIV Fusion Inhibitory Property Based on Gp41 Interaction Assay.
abstract: BACKGROUND
  Gp41 of HIV (Human Immunodeficiency Virus) is a protein that mediates fusion between viral and cellular membranes. The agent, T-20, which has been approved for HIV inhibition, can restrain Gp41 function in the fusion process; nevertheless, it has disadvantages like instability, high cost of production and injection form to be delivered twice a day.
  
  
  METHODS
  Several molecules like NB-2 and NB-64 have been discovered that can inhibit HIV infection. These molecules were used as template compounds to design and develop more effective small molecules functioning as HIV-1 fusion inhibitors targeting Gp41. The process included in silico docking protocols using HEX and ArgusLab applications. A multisource database was created, after choosing the best molecules; they were tested in vitro for inhibitory activity by HIV-1 single-cycle model, transfected in HEK cells (293T).
  
  
  RESULTS
  Computational analysis and experimental data were combined to explore molecular properties and the most potent ones were found, with the best suitable criteria for interaction with Gp41. Several examples (DAA-6, DAA-9 and DAA-12) could inhibit infection in vitro as effective as NB-2, NB-64.
  
  
  CONCLUSIONS
  Since disadvantages of available fusion inhibitor (T-20), it seems necessary to find similar molecules to be approved and have small size providing suitable bioactivity profile. The molecules explored in this study can be good candidates for further investigations to be used as oral HIV fusion inhibitors in the future.
authors.affiliation: Department of Medical Biotechnology, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: Soroush
authors.initials: S
authors.lastname: Sardari
authors.forename: Kayhan
authors.initials: K
authors.lastname: Azadmanesh
authors.forename: Fereidoun
authors.initials: F
authors.lastname: Mahboudi
authors.forename: Asghar
authors.initials: A
authors.lastname: Davood
authors.forename: Ruhollah
authors.initials: R
authors.lastname: Vahabpour
authors.forename: Rezvan
authors.initials: R
authors.lastname: Zabihollahi
authors.forename: Hosna
authors.initials: H
authors.lastname: Gomari
keywords: Antagonists and inhibitors; Drug design; Flow cytometry; HIV fusion inhibitors